RAG1およびRAG2タンパク質によるDNAトランスポーゼーション:腫瘍性トランスロケーションの潜在的な源
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.
Cell
|September 4, 1998
まとめ
RAG1およびRAG2タンパク質はV(D) J再結合を開始し,DNAセグメントを移動させることもでき,免疫システムは移動性DNA要素から進化したことを示唆しています. この転置活性が,リンパ性腫瘍における特定のDNA転位を説明する可能性がある.
科学分野:
- 分子生物学は分子生物学である.
- 免疫学 免疫学とは
- 遺伝学 遺伝学とは
背景:
- RAG1およびRAG2タンパク質は,適応免疫にとって重要なプロセスであるV(D) J再結合に不可欠です.
- V(D) J再結合は,再結合信号配列 (RSS) と呼ばれる特定のDNA部位で二重鎖の断裂を生成することを含む.
研究 の 目的:
- RAG1およびRAG2タンパク質のV(D) J再結合を超えた完全な触媒的能力を調査する.
- V(D) J再結合システムの進化的起源を探求する.
- ゲノム不安定性と疾患におけるRAG媒介トランスポジションの潜在的な役割を理解する.
主な方法:
- 精製されたRAG1およびRAG2タンパク質の活性を分析するために生化学的測定を用いた.
- RSSとコーディング配列を含むDNA基板は,再結合と転置活動のテストに使用されました.
- 挿入部位と反応機構を特定するためにDNA製品の分析.
主要な成果:
- RAG1とRAG2のタンパク質は,V(D) J再結合だけでなく,転置反応を触媒として作用することが示されました.
- 分裂したRSSは,結合反応でRAGタンパク質によって新しいDNA部位に挿入されることが示されました.
- このRAG媒介のDNA転送は,移動性DNA要素からのV(D) J再結合の進化の証拠を提供します.
結論:
- V(D) J再結合システムは,古代のDNAトランポゾンから進化した可能性が高い.
- 繰り返されたトランポジションイベントは,抗原受容体遺伝子ロケーションの拡張に寄与している可能性があります.
- 異常なRAG媒介トランポジションは,リンパ性悪性腫瘍で観察された特定のDNA転位の病原性に関与している可能性があります.
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